Overweight or obesity is an established negative prognostic factor in both pre-menopausal and postmenopausal breast cancer, and several mechanisms have been proposed to explain this observation. One possible mechanism relates to the effect of excess adipose tissue on circulating gonadal hormones, because adipose tissue is an important extragonadal source of estrogens from precursor adrenal androgens. Obesity is associated with increased circulating concentrations of estrone and estradiol in postmenopausal women, and it also is associated with decreased levels of sex-hormone binding globulin (SHBG), which increases the bioavailable estrogen fraction Another possible mechanism relates to insulin and insulin-like growth factor (IGF)-I, and the interactions of these factors with adiposity and weight Circulating insulin concentration is highly correlated with degree of adiposity in breast cancer survivors In an ongoing NCI-funded randomized controlled study, we are testing the effect of a multi-component weight reduction program on change in body weight and body composition in overweight and obese breast cancer survivors (n=85), and blood samples are collected from the study participants at baseline, 16 weeks (after the intensive treatment phase), and one year. The intervention incorporates cognitive-behavioral therapy, increased physical activity to promote maintenance of (or increased) lean body mass, diet modification to facilitate an energy imbalance, and strategies to improve body image and self-acceptance. The aims of the proposed small grant project are (1) To conduct laboratory assays of SHBG and serum estrogens, and to examine the effect of the intervention on these hormonal factors, in breast cancer survivors participating in a weight reduction program (compared to women in a wait-list control group), using stored blood samples collected at enrollment and following participation, and (2) To conduct laboratory assays of serum insulin, total IGF-I, free IGF-I, and a key binding protein (IGFBP-3) and to examine the effect of the intervention on these hormonal factors in breast cancer survivors participating in the program (compared to women in a wait-list control group), using stored blood samples collected at enrollment and following participation The measurement of hormonal factors and data analyzed in this project will provide vital information about the responsiveness of these hormonal factors to weight loss and change in body composition in overweight and obese breast cancer survivors Also, the results from this study will provide valuable insight about possible mechanisms by which overweight or obesity influences prognosis in women who have been diagnosed with breast cancer.